[1] Background art on desalting purification of an aqueous solution of an alkali metal salt of amino acid:
The method for producing an amino acid, such as glycine or alanine, which comprises reacting cyanohydrin with ammonia and hydrolyzing aminonitrile corresponding to the resulting amino acid (glycinonitrile in the case of glycine and aminopropionitrile in the case of alanine) is known as a Strecker reaction. The method is disclosed, for example, in JP-B-29-8677, JP-B-59-28543, JP-B-51-24481, JP-B-43-29929 and JP-B-51-40044. In the Strecker method, amino acid is obtained in the form of an alkali metal salt.
As a method for producing amino acid from the resulting aqueous solution of alkali metal salt of amino acid, there has been proposed a method which comprises neutralizing the aqueous solution of alkali metal salt of amino acid with sulfuric acid and thereafter recovering amino acid by crystallization method. According to the crystallization method, because inorganic salts, such as sodium sulfate and sodium chloride, which are produced, for example, in purification of an aqueous solution of sodium salt of glycine, are very similar to glycine in solubility, the amino acid, namely, glycine, cannot be sufficiently recovered by one-stage crystallization. Therefore, the following various methods have been proposed. That is, there are methods which carry out a series of troublesome operations such as crystallization of a part of the inorganic salt by troublesome adjustment of pH, crystallization of a part of iminodiacetic acid, and crystallization of glycine (see, for example, JP-B-58-8383, Japanese Patent No. 1179351 and JP-A-52-118421); and methods which repeat a plurality of times the operation of crystallizing a part of sodium sulfate at high temperatures and then crystallizing glycine at low temperatures (see, for example, JP-B-57-53775). However, all of these methods are very troublesome in operation and low in productivity, and can hardly be industrially employed.
On the other hand, there have been proposed methods of obtaining an aqueous amino acid solution by subjecting alkali metal ions in an aqueous solution of alkali metal salt of amino acid to cation exchanging (desalting) using a cation exchange resin. Methods using weakly acidic cation exchange resins are disclosed in JP-B-29-8677, JP-B-36-21315 and JP-A-2003-221370, and a method of using a strongly acidic cation exchange resin is disclosed in JP-B-7-68191.
In general, the ion exchange resins used are required to have a different adsorbability for alkali metals than adsorbability for amino groups of amino acid, namely, have selectivity in adsorption for them. Therefore, in order to avoid adsorption of amino groups of amino acid to the resin as much as possible, weakly acidic cation exchange resins will be suitable.
Furthermore, as for ion exchange apparatuses using ion exchange resins, there are proposals to reduce the absolute amount of the resin used and improve ion exchange efficiency and regeneration efficiency by continuously moving the resin as compared with a fixed bed type (a moving bed type continuous ion exchange apparatus). For example, a method of moving bed type is proposed according to which a column through which a solution is passed for ion exchange, a column for regeneration, and a column for water washing are organically connected; the resin is automatically discharged by passing the solution under internal pressure of the column, and transferred to the hopper of the next column; then, a resin, in an amount corresponding to the amount of the resin discharged due to reduction of internal pressure of the column caused by extraction of the solution, is introduced into the column from the upper hopper, and the resin, in an amount corresponding to the amount of resin introduced, is automatically and gradually transferred to the hopper from the other column under the internal pressure of the column so as to return to the initial state of solution passing; and this operation is repeated to continuously transfer the resin (see JP-B-38-5104 and Shozo Miyahara, Takaaki Omagari and Shigeo Sakai, “Practical Ion Exchange” pp 74-88 (1972) (Kagaku Kogyosha)).
However, the desalting purification using a moving bed type continuous ion exchange apparatus has been utilized solely for recovery from a dilute ion solution. That is, there have been no proposals to carry out ion exchange from high concentration ion solution, such as desalting purification of an aqueous solution of alkali metal salt of amino acid, by a moving type continuous ion exchange apparatus.
As mentioned above, when desalting purification of an aqueous solution of alkali metal salt of amino acid such as glycine or alanine is carried out using an ion exchange resin, it is advantageous to use a weakly acidic cation exchange resin of H-form, taking into consideration a decrease in product recovery efficiency due to adsorption of amino acid. However, it is known that the weakly acidic cation exchange resin expands (or swells). Generally, strongly acidic cation exchange resins having sulfonic groups as functional groups and comprising a styrene resin as a matrix do not utterly expand (rather contract) in the case of exchanging from H-form to Na-form. On the other hand, it has been reported that, for example, weakly acidic cation exchange resins having carboxylic groups as functional groups and comprising a methacrylic resin as a matrix are 90% in swelling ratio (increase to 1.9 times in volume) in exchanging from H-form to Na-form, and weakly acidic cation exchange resins comprising an acrylic resin as a matrix are 50% in swelling ratio (increase to 1.5 times in volume). When generally employed fixed bed type apparatus is industrially utilized as an ion exchange process, there are the following defects. That is, when the resin abruptly expands in volume, drifting of the solution occurs causing a decrease of ion exchanging reaction efficiency, and furthermore, an extravagant pressure is applied to the resin in the lower part of the column causing serious damage of the resin. Therefore, ion exchange efficiency decreases and frequent addition of the resin is necessary. Moreover, there is a possibility of deformation or breakage of the exchanging column by the pressure generated by expansion of the resin, and special structures are required in the design of exchange apparatuses that consider strength, supply of solution, and recovery of solution.
Thus, use of weakly acidic cation exchange resins causes various problems such as decrease in exchange efficiency and water washing efficiency due to the expansion of the resin, care on inserts and strength in designing of the exchanging column, and the necessity of adding resin owing to damages of the resin. These problems are disadvantageous in industrially carrying out the desalting purification of an aqueous solution of alkali metal salt of amino acid using fixed bed type ion exchange apparatuses. In addition, for purification of amino acid which is to be commercialized finally as a solid, it is necessary to subject to the exchange treatment the solution of raw material (solution to be treated) at a concentration as high as possible and to carry out efficient purification utilizing all of the ion exchange groups. Therefore, when desalting purification of an aqueous solution of alkali metal salt of amino acid is carried out with fixed bed type ion exchange apparatuses, the expansion of the resin occurs throughout the exchanging column and thus, problems caused by the expansion of the resin occur conspicuously.
Moreover, generally, in carrying out ion exchange with fixed type ion exchange apparatuses, passing of the solution is stopped when the concentration of the alkali metal reaches a given value in the aqueous amino acid solution obtained as a product (namely, at a break through point of the ion exchange resin). In this case, the solution to be treated (the raw material) remains in the ion exchanging column as a solution carried by the resin (1 m3 of ion exchange resin contains 0.5 m3 of void water), and for recovery of the solution, pure water is supplied to carry out replacement (forcing out) and water washing. This water used for the water washing contains active ingredients, which are recovered as raw materials, and as a result, the raw materials are diluted. Furthermore, after regeneration of the resin, the resin is similarly washed with water to remove the mineral acids and mineral acid alkali metal salts used as regenerating agents, and then the passing of solution is restarted. In this case, the aqueous solution of the product amino acid is unavoidably diluted than the concentration of the raw material with void water contained in the H-form resin (although the void water can be abandoned before the product amino acid begins to be discharged). The amino acid is usually commercialized as solid, and hence water must be recovered and much dilution is industrially disadvantageous.
Moreover, in carrying out the ion exchange treatment by fixed bed type ion exchange apparatuses, the above-mentioned operation is generally employed, and there occurs unavoidably some leakage of the alkali metal salt into the aqueous solution of the product amino acid. When it is attempted to inhibit the leakage, the exchange treatment is required to terminate before the effective utilization of the tip portion of the packed ion exchange resin. That is, amino groups of the amino acid are partially exchanged and adsorbed to the tip portion of the ion exchange resin column. If the replacement by water washing is carried out excessively, since there is a problem of dilution, the resin to which amino acid partially adsorbs is carried to the regeneration step, which leads to loss of useful amino acid. This further brings about an increase of environmental load due to wastes. For avoiding this problem, JP-A-2003-221370 proposes a method of further feeding the alkali metal salt of amino acid after reaching the break through point and reports that the concentration of amino acid (glycine) in the solution subjected to regeneration treatment is reduced to 110 ppm/SO4. However, this method suffers from the problem of an increase in the amount of the raw material recycled. Moreover, the problem of leakage of alkali metal in the product has not been solved, and the concentration of sodium ion in the product amino acid (glycine) corresponds to 240 wtppm/glycine.
Depending on the production method, the ion exchange resins include those in which one spherical particle is formed by agglomeration of microspheres as a base matrix and those which have a three-dimensional network structure, but have a base matrix which is dense and high in physical strength due to the content of crosslinking agent. The former has a space volume produced by agglomeration of microspheres and hence is high in diffusion rate and ion exchange rate, but low in resin strength and unavoidably has the defects caused by the resin expansion. The latter is somewhat superior in resin strength and hence, is expected to have less problems caused by the resin expansion; but since the base matrix is dense, the resin has a low ion exchange rate and a small selectivity for adsorption of alkali metal and amino group of amino acid, therefore it is difficult to perform efficient recovery of the product amino acid with fixed bed type ion exchange apparatuses.
[2] Background art on separation and recovery of amino acid and iminodicarboxylic acid:
In producing amino acid by Strecker method, there is a demand to separate and recover simultaneously and at high purity the iminodicarboxylic acid, which is a by-product in the reaction, and the amino acid, which is a product. As mentioned above, the attempt to purify amino acid by crystallization method has not succeeded in the conventional technologies.
A method of crystallization and recovery of amino acid as a copper salt has been proposed, but this method requires troublesome operation for removing copper (see, for example, JP-A-59-118747). According to a method of utilizing an electrodialysis with ion-exchange membranes, amino acid of high purity can be obtained. However, amino acid permeates through the membrane and is contained in the discharged solution, and membranes through which only multivalent ions of iminodicarboxylic acid selectively permeate have not been developed, and hence, the above method cannot be industrially utilized (see, for example, JP-A-51-34114).
Furthermore, a method of adsorbing amino acid to H-form strongly acidic cation exchange resins and thereafter separating the amino acid has been proposed (see, for example, JP-A-58-210027). This is conducted in a laboratory, but requires a large amount of ion exchange resins for adsorption of a large amount of amino acid, and can hardly be industrially employed. A method of carrying out chromatographic separation using strongly acidic cation exchange resins of salt form has been proposed (see, for example, JP-A-2-215746), but it is difficult to continuously treat a large amount of a solution in industrial scale, and a great number of ion exchange columns are required. Any of these conventional technologies have no disclosures of a process in which amino acid and iminodiacetic acid can be simultaneously separated and recovered at high purity and high yield.
Furthermore, there has been proposed a method according to which sodium ions of an aqueous solution of sodium salt of amino acid are subjected to cation exchanging (desalting) using a cation exchange resin to obtain an aqueous solution of crude glycine containing a colored substance, followed by treating with a weakly basic anion exchange resin or a medium basic ion exchange resin (see, for example, JP-B-54-1686).
This document has no disclosure on purity (residue of impurity) of the resulting amino acid (glycine), but discloses that the loss of glycine adsorbed to the ion exchange resin is about 0.2-1.5%. The purity of the resulting amino acid is kept by stopping the passing of solution when the concentration of organic acid (iminodiacetic acid, glycolic acid, formic acid) contained reaches a specified value, namely, a break through point at which the organic acid in a given amount leaks in anion exchanging. In this case, since the break through point in adsorption of organic acid is not a saturated adsorption point of the anion exchange resin, the organic acid does not adsorb with saturation to the tip of the anion exchange resin, and there is an ion exchange region which has not been subjected to exchanging. That is, in this ion exchange region, anions of amino acid are ion exchanged and adsorbed to the anion exchange resin in addition to OH-form anions.
When this ion exchange region is regenerated with an alkali metal salt, anions in amino acid are ion exchanged and carried together with the regeneration solution, resulting in recovery loss of amino acid. Moreover, the recovery solution contains iminodiacetic acid in a large amount, and iminodiacetic acid can be produced as a product. However, amino acid incorporates into the product as an impurity, and thus complicated operation is necessary.
Furthermore, in general, iminodiacetic acid adsorbed to the resin in the column is liberated by chromatographic separation and regeneration with a solution of a base which is sodium hydroxide, and hence, iminodiacetic acid is obtained in the form of a sodium salt. Therefore, in the case when a product iminodiacetic acid in the form of an acid is desired, a purification step is further needed, which greatly affects the cost.
[3] Background art on purification of glycine:
Amino acids, especially glycine, are widely used as raw materials for food additives of processed foods, medicines, and agricultural chemicals.
The background art relates to a method for production of glycine, in more detail, a method for optionally producing glycine in a desired crystal form. The crystal forms of glycine include the three forms of α, β, γ types (see, for example, “J. Amer. Chem. Soc.” 61, 1087 (1939) and “Proc. Japan Acad.” 30, 109 (1954)). There is a demand for a method of optionally purifying glycine to a desired form (α-type glycine or γ-type glycine).
As a method for industrial isolation of glycine, concentration crystallization, cooling crystallization, solvent crystallization, and the like are generally carried out, and the product is commercialized as α-type glycine. The α-type glycine is high in luminance and smaller in average particle diameter than γ-type glycine, and hence, is demanded to be commercialized from the viewpoint of the uses for food additives, etc.
However, it has become clear that this α-type glycine is apt to firmly consolidate in the form of rocks during storage, which causes serious problems in production, distribution and storage, and uses. This is due to the transition of α-type glycine to γ-type glycine in the presence of water.
Under the circumstances, in order to avoid the problem of consolidation of α-type glycine, there has been proposed a method of previously obtaining glycine as γ-type glycine. For example, JP-B-2-9018 discloses a method for producing γ-crystal glycine by inoculating γ-crystal in a saturated solution of glycine and gradually cooling the solution while stirring. This is a proposal that γ-type glycine can be produced by inoculating γ-type glycine in a saturated solution of glycine. However, according to the example given in the patent document, it is disclosed that the method is fundamentally batch-wise, and γ-type glycine is stably obtained when the cooling rate is 5° C./Hr while α-type glycine is produced when the cooling rate is 50° C./Hr. That is, it is presumed that a mixture of α-type glycine and γ-type glycine is obtained depending on the gradual heating rate. γ-type glycine is stably obtained under the conditions of a gentle cooling rate of 5° C./Hr, and when the method is industrially carried out, a large-sized crystallizing cell or many crystallizing cells are required, which is disadvantageous. In order to selectively produce only the desired crystal form of α-type glycine or γ-type glycine, the gradual heating rate must be accurately controlled. Moreover, the patent document is silent on the quality of water used for crystallization. (Hereinafter, “α-type glycine” and “γ-type glycine” are sometimes referred to as merely “α-type” and “γ-type”, respectively.)
JP-A-9-67322 reports a method for producing γ-type glycine under quenching comprising keeping the degree of supersaturation in operation in the crystallizing cell at 0.1-2.0 g glycine/100 g water. However, this method also requires severe control of the degree of supersaturation. It is disclosed in the specification that if it deviates from the range of control, a mixed type glycine of α-type and γ-type is obtained, and this is not satisfactory as a method for industrial production of glycine having the desired crystal form. Moreover, this patent document makes no mention of the quality of water used for crystallization.
Moreover, there has been proposed a method of converting crystallized α-type glycine to γ-type glycine.
For example, JP-B-2-9019 proposes that α-type glycine in the state of crystal, which is kept coexistent with γ-type glycine and water, be converted to γ-type glycine. However, as mentioned in this patent document, the method has the defects that agglomeration and consolidation are apt to occur during conversion of α-type glycine to γ-type glycine, and troublesome operations such as grinding are required for obtaining γ-type glycine as commercialized products by industrially carrying out the method. Moreover, the patent document makes no mention of the quality of water used for crystallization.
JP-A-9-3015 proposes that α-type glycine is kept in an aqueous solution having a pH of 7-14 and converted to γ-type glycine in the state of crystal. However, as mentioned above, there are problems that agglomeration and consolidation are apt to occur during conversion of α-type glycine to γ-type glycine, and troublesome operations such as grinding are required for obtaining γ-type glycine as commercialized products by industrially carrying out the method. Furthermore, the patent document proposes to add hydroxides, carbonates, or oxides of alkali metals or alkaline earth metals to aqueous glycine solution. However, the object of the addition is merely to convert α-type glycine to γ-type glycine by adjusting the pH of the aqueous glycine solution to 7-14. In the examples given in the patent document, only sodium hydroxide was used.